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. 2020 Sep 27;9(10):3120. doi: 10.3390/jcm9103120

Table 3.

Efficacy of melflufen combination therapies in patients with multi-refractory multiple myeloma [51,52,56,57].

Study Treatment Patients, n Prior Therapies, Median (Range) Median Follow-Up, mo ORR, % Median PFS (95% CI), mo Safety Profile
O-12-M1
(Phase I/II)		 Melflufen + dexamethasone;
median duration:4.1 mo		 45
(Phase II; evaluable for response)		 4 (2–14) 27.9 31 5.7
(3.7–9.2)

  • Any-grade AEs: 100%

  • Melflufen-related Grade ≥3 AEs: 82%

  • Study cycle length increase allowed for full hematologic recovery and reduced the frequency of Grade 4 thrombocytopenia

  • SAEs: 38%

  • Treatment-related SAEs: 27%

  • Most common nonhematologic AEs (≥20%): pyrexia, asthenia, fatigue, nausea, and diarrhea

  • Most common treatment-related SAE (≥5%): pneumonia (9%)
HORIZON *
(Phase II)		 Melflufen + dexamethasone;
median duration: 14.3 wk		 154
(125 evaluable for response)		 5 (2–12) Not reported 29 4.2
(3.7–4.9)

  • Any-grade AEs: 97%

  • Grades 3/4 AEs: 85%

  • Treatment-related SAEs (≥5%): infections and infestations (5%), febrile neutropenia (5%)
ANCHOR †
(Phase I/II)		 Melflufen (30 or 40 mg) + dexamethasone + daratumumab;
median duration: 6.2 mo		 33
(30 mg, n = 6; 40 mg, n = 27)		 30 mg: 2.5 (1–3)
40 mg: 2.0 (1–4)		 6.6 76 14.3
(9.7-NR)

  • No DLTs

  • Treatment-related Grade 3/4 AEs: 82% (83% and 81%)

  • SAEs: 36%

  • Treatment-related SAEs: 18%

  • Treatment-related SAEs (≥5%): febrile neutropenia (6%)
Melflufen (30 or 40 mg) + dexamethasone + bortezomib;
median duration: 9.3 mo		 6
(30 mg or 40 mg, n = 3 each)		 2.5 (2–4) 13.4 67 NR

  • No DLTs

  • SAEs: 83%

  • Treatment-related SAEs: 17%

  • Treatment-related SAEs: pneumonia and neutropenia (n = 1)

* Patients received 40 mg melflufen (Day 1) plus 40 mg dexamethasone (20 mg if aged ≥75 years) weekly (Days 1, 8, 15, and 22) of each 28-day cycle. † In the daratumumab arm, patients received melflufen (Day 1) plus 40 mg dexamethasone weekly (Days 1, 8, 15, and 22 of each cycle and an additional dose on Day 2 of Cycle 1), plus 16 mg/kg daratumumab (Days 2, 8, 15, and 22 in Cycle 1; Days 1, 8, 15, and 22 in Cycle 2; Days 1 and 15 in Cycles 3–6; and Day 1 in Cycle 7 and beyond). In the bortezomib arm, patients received melflufen (Day 1) plus dexamethasone (20 mg on Days 1, 4, 8, and 11; and 40 mg on Days 15 and 22), plus 1.3 mg/m2 bortezomib (Days 1, 4, 8, and 11). AE, adverse event; DLT, dose-limiting toxicity; NR, not reached; ORR, overall response rate (≥partial response); PFS, progression-free survival; SAE, serious AE.